Variant X-67546514-TGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGC-TGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGC details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1BS2

The NM_000044.6(AR):c.1409_1420dup(p.Gly470_Gly473dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. G456G) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0067 ( 6 hom., 59 hem., cov: 0)

Exomes 𝑓: 0.0014 ( 5 hom. 208 hem. )

Failed GnomAD Quality Control

Consequence

AR
NM_000044.6 inframe_insertion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.29

Variant links:

Genes affected

AR (HGNC:644): (androgen receptor) The androgen receptor gene is more than 90 kb long and codes for a protein that has 3 major functional domains: the N-terminal domain, DNA-binding domain, and androgen-binding domain. The protein functions as a steroid-hormone activated transcription factor. Upon binding the hormone ligand, the receptor dissociates from accessory proteins, translocates into the nucleus, dimerizes, and then stimulates transcription of androgen responsive genes. This gene contains 2 polymorphic trinucleotide repeat segments that encode polyglutamine and polyglycine tracts in the N-terminal transactivation domain of its protein. Expansion of the polyglutamine tract from the normal 9-34 repeats to the pathogenic 38-62 repeats causes spinal bulbar muscular atrophy (SBMA, also known as Kennedy's disease). Mutations in this gene are also associated with complete androgen insensitivity (CAIS). Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jan 2017]

AR links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00672 (558/83059) while in subpopulation AFR AF= 0.0199 (432/21655). AF 95% confidence interval is 0.0184. There are 6 homozygotes in gnomad4. There are 59 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 6 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AR	NM_000044.6 linkuse as main transcript	c.1409_1420dup	p.Gly470_Gly473dup	inframe_insertion	1/8	ENST00000374690.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AR	ENST00000374690.9 linkuse as main transcript	c.1409_1420dup	p.Gly470_Gly473dup	inframe_insertion	1/8	1	NM_000044.6	P1	P10275-1

Frequencies

GnomAD3 genomes

AF:

0.00672

AC:

558

AN:

83055

Hom.:

Cov.:

AF XY:

0.00355

AC XY:

AN XY:

16621

show subpopulations

Gnomad AFR

AF:

0.0200

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00577

Gnomad ASJ

AF:

0.00405

Gnomad EAS

AF:

0.00194

Gnomad SAS

AF:

0.00196

Gnomad FIN

AF:

0.000420

Gnomad MID

AF:

0.0103

Gnomad NFE

AF:

0.00125

Gnomad OTH

AF:

0.00660

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00138

AC:

657

AN:

476223

Hom.:

Cov.:

AF XY:

0.00176

AC XY:

208

AN XY:

118245

show subpopulations

Gnomad4 AFR exome

AF:

0.00923

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000314

Gnomad4 EAS exome

AF:

0.000284

Gnomad4 SAS exome

AF:

0.00163

Gnomad4 FIN exome

AF:

0.0000457

Gnomad4 NFE exome

AF:

0.00127

Gnomad4 OTH exome

AF:

0.00131

GnomAD4 genome

AF:

0.00672

AC:

558

AN:

83059

Hom.:

Cov.:

AF XY:

0.00355

AC XY:

AN XY:

16631

show subpopulations

Gnomad4 AFR

AF:

0.0199

Gnomad4 AMR

AF:

0.00576

Gnomad4 ASJ

AF:

0.00405

Gnomad4 EAS

AF:

0.00195

Gnomad4 SAS

AF:

0.00197

Gnomad4 FIN

AF:

0.000420

Gnomad4 NFE

AF:

0.00125

Gnomad4 OTH

AF:

0.00651

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over